If statins are so safe, why won’t some researchers let us see their data?

A couple of weeks ago one of my blog posts focused on a news story regarding the safety of statins. We were informed that ‘new evidence’ had found, except in rare circumstances, statins are no more hazardous than placebos. Yet, when one pays to get access to the actual paper on which these ‘conclusions’ were based (as I did), one realises that the authors of this paper list 6 separate reasons why statin safety data is not to be relied upon. In particular, there are several reasons why the true risk of side effects may be higher than the (inadequate) data would suggest. In this context, what compelled the lead author of the study to issue such strenuous reassurances about the safety of statins remains a mystery to me.

I got a feeling of déjà vu this week, on reading this story. Professor Rory Collins tells us that concerns about the potential hazards of statins is misguided and is putting lives at risk. The underlying message seems to be that people should just shut up, take their statins, and be grateful for this wonder drug.

The research group to which Professor Collins belongs (the Cholesterol Treatment Trialists or ‘CTT’) is tasked with conducting research on statin drugs. Mainly, it pools together the results of industry-funded statin studies, and then occasionally makes pronouncements on this class of drugs. I don’t think I would be mischaracterising the CTT to say that it is a staunchly pro-statin body (or lobby group).

However, if you wanted to see for yourself the data on which the CTT researchers base their edicts, you’d be sorely disappointed. That’s because despite repeatedly being asked for it, the CTT researchers have steadfastly refused to cough it up. Why this should be is anyone’s guess, but the CTT researchers’ stance appears to be that we’ll just have to trust them.

This strategy may have worked like a charm 20 years ago, when people really had no choice but to take what ‘key opinion leaders’ said at face value. These days, though, things are a bit different. The advent of the internet means that almost anyone can find reports of statin side effects as well as information on why the evidence base in this area is incomplete and/or hidden. I think a couple of decades back, the general reaction to Professor Collins’ comments would likely have been ‘well, he must know what he’s talking about – he is a professor, after all.’ While some may have this reaction today, my suspicion is that these will be outnumbered by people who think that Professor Collins dost protest too much.

Of course, it might be that Professor Collins truly believes what he says. He may, for instance, be utterly unaware of the reasons why the evidence base may not accurately reflect what goes on in the real world. Here are just four such reasons:

1. the evidence is taken from short studies or studies that have been terminated early (things that tend to lead give a falsely low impression of risks and also an exaggerated impression of benefits)

2. the screening out those susceptible to side effects before the study begins

3. the logging of side effects only if there’s been an extreme deviation from normal biochemistry (some studies only log side effects once biochemical markers are several times the upper limit of normal)

4. not looking for and logging side effects in the first place

For someone who is an expert in statins and research, though, ignorance of the issues is unlikely here (though not utterly implausible). Given his position, I’d say if Professor Collins is ignorant of the issues, then he is failing in his duty to keep abreast of the area, in order that he can give balanced and impartial advice about statins.

Assuming, for a moment, that Professor Collins actually understands the deficiencies of the evidence base, what logical conclusions might drawn?

Some may get the distinct impression that Professor Collins is hopelessly biased. Perhaps he has some reason for bigging up statins at every opportunity, while downplaying the risks. Certainly, Professor Collins has conflicts of interest. Here you will see that he has been “engaged in research activities for Merck, Bristol-Myers Squibb, Sanofi, and AstraZeneca.” This does not mean his judgement is ‘clouded’, but it’s reasonable to wonder if it might have been.

And what of the claim that concerns about the side-effects of statins are putting lives as risk? The recent furore around statins appears to have been sparked by a proposed move here in the UK for doctors to consider people as candidates for statins if their risk of developing cardiovascular disease over the next decade is 10 per cent of more (as opposed to the current cut-off of 20 per cent for more over the next decade). However, we already know that in people without a history of cardiovascular disease, statins do not save lives. Extendingtreatment to those at even lower risk will not save lives either. If these people come to conclude that the risks of statins outweigh the benefit for them as an individual, they are simply not risking their lives at all.

If I had a personal message for Professor Rory Collins it would be perhaps to point out that the world has moved on since the CTT group was set up, and that the public has grown increasingly well informed and sophisticated. No longer can ‘experts’ make pronouncements without fear of being questioned or challenged.

Most importantly, though, not giving people the full facts does not allow them to make informed decisions, and actually can risk the health and wellbeing large swathes of the population. The CTT’s refusal to give up their data so that it can be independently analysed simply cannot be in the interests of patients, and may lead to some putting their health needlessly at risk of one or more of the recognised adverse effects of statins including fatigue, pain, liver damage, kidney damage and mental symptoms.

Maybe Professor Collins is unaware of the potential damage his comments may do in this respect. If so, he should at least be aware of the damage he may be doing to his own reputation by statements which, some might say, appear institutionally biased and are demonstrably misleading.

28 Responses to If statins are so safe, why won’t some researchers let us see their data?

When Professor Collins came on the radio and dubbed those who were skeptical about statins effective murderers, the status of his dispassionate veracity became very clear in my mind. As, I’m sure, in most reasonable people’s minds.

Of all the tricks that industry studies play, this one is the most audacious:
“the screening out those susceptible to side effects before the study begins”.

That’s like conducting a study which proves that people almost never get heads when a coin is tossed. And starting the study by scrubbing the Queen’s head off most of the test coins first.

When I heard Sir Rory’s rude and aggressive tone on the radio last Saturday, lambasting the BMJ as “irresponsible” for publishing research which found that statins caused harmful side-effects and did not reduce mortality, my first thought was to wonder who funded his research was funded. I was not at all surporised to find that its extensively funded by industry!

The evidence for statin use is on very thin grounds, also for secondary prevention I’d say. As you mention, stopping trials early for benefit which is a massive problem in many of these trials both for benefit and harm. IMO one should always respect the trial’s prespecified duration unless there are overwhelming benefits — benefits that statins fail to produce.

The evidence for statin use in secondary prevention is probably exaggerated. GREACE was a horribly designed study and should not be cited, 4S has never even come close to being replicated despite tons of statin studies conducted since, LIPID was terminated before its prespecified duration and the use of allocation concealment was unclear, CARE found no statistically significant differences in CHD death and almost no difference total mortality. What are we to make of Professor Collins HPS study? Given the lack of transparency I’d also be skeptical of the modest 13% reduction in mortality and subgroup findings that have never confirmed (e.g. diabetics, elderly, women).

I’d say the use of statins in any group is doubtful given the probable exaggerated benefits and underestimated harms.

Just can say after researchers in Sweden have declared statins as useless, I dropped mine. Just ask the docs to measure the Apo level of LDL. Send me his e-mail address and I will ask him also. Im on two “researchers” that felt attackt when I ask it they are payed by some of the med companies to tell the Swedish population that high amount cholesterol are bad.

Hej Micke, my mum in Sweden tried 3 types of statins before finding one that didnt give her too many sidefects. She started taking these without my knowledge and I find it very hard to tell her now that it is infact harmful (or could be). Could you post a link please for the Swedish info.

I have decided that it is better to reverse the health advice given by ‘authorities’ as it’s usually quite wrong and given to increase incidence of profitable illness – not to make the population healthy.

Nice post Dr Briffa. Discussing statin drugs, their use and side effects I can see is a passion, and understandably so. If I can make a request, if possible in a future post or two would you bring up your thoughts on ways to address heart disease risks?

I mention this somewhat jokingly, but over the years the impression I’ve gathered is that for many visiting a doctors office is an event. The different tests doctors order, results given, and prescriptions written are often items to discuss with family and friends. Little thought is often given for the value of these tests. The joking part I have is that sometimes when I hear these discussions, it is almost as if people are reliving childhood school days. Doctors could do well if they placed gold stars on test result papers providing a grade. Of course a red stamped frown face would be a big disappointment.

What other heart disease tests can be arranged that people can talk about? What life style changes, diet, supplements, even prescriptions can be made that would be helpful? I think many are looking to take charge of their health further, beyond the typical. Just some thoughts had this evening.

This all seems very one-sided, so, just to balance the discussion (for those whose minds are not made up).

1. CTT is funded by organisations with no conflicts of interest; organisations such as the Medical Research Council, the British Heart Foundation, and Cancer Research UK. CTT produce high quality evidence to help inform healthcare decisions, they are not a lobby group.

2. Of course many of the statin trials were industry-funded. Do we expect the public or charities to pay for studies when the statins in question were still under patent? To avoid the issues of conflicts of interests many statin studies have been funded by industry but performed and analysed by independent clinical trials units (which don’t have conflicts of interest).

3. Professor Collins works for Oxford University’s Clinical Trial Service Unit (CTSU). He was a lead investigator on the Heart Protection Study (HPS) where over 20,000 patients took simvastatin 40mg or placebo for over five years, and were then followed up afterwards to give a total follow up of around 11 years. Not exactly one of these ‘short studies or studies that have been terminated early’. There are many HPS-related publications. Most papers can be found here:http://www.ctsu.ox.ac.uk/~hps/
And here’s the one which relates to the long-term follow up, after the trial treatments finished:http://www.sciencedirect.com/science/article/pii/S0140673611611252

As for point 2: considering the data-hiding and trial manipulations that the industry has frequently been caught doing, your question is fallacious. Merely because we might resent paying for the trials out of public funds does not suddenly make them valid.

3. And why do Professor Collins and colleagues always refused to show the Kaplan Meier MORTALITY CURVES (not the total number only) of the HPS study if he is so confident about the benefits of the simvastatin ?
|”Something rotten in the kingdom of Dr Collins ?*

There are also other points that make me suspicious of the HPS results:

The HPS trial never reported the results for all four groups separately which is imperative in a factorial trial. For example, look at how the results of GISSI-P were reported compared to HPS.

A pre-randomization phase was used in HPS which excluded a ton of people (Dr. Briffa’s point 2).

The alleged benefits that were found in numerous subgroups have never been confirmed. The 13% reduction in mortality would be expected to apply to all subgroups, yet such benefits are not seen in properly conducted trials (non-truncated) directly testing the relevant hypotheses.

The HPS has bias written all over it and this would include Professor Collins.

To Z.M., I totally agree with you, however the 13% decrease in mortality is the relative risk. The absolute risk decrease is 1.8% (14.7% on placebo minus 12.9% on statin) for the duration of 6 years, thus the 6-year NNT is 55 pt-years or an annualized NNT of 333 pt-years; therefore if 333 pts take simvastatin 40 mg for onr year , they will live on average 26 hours more ((but probably with myalgia, diabetes, loss of memory,….)

or another way to put it (if you totally believe in Dr Collins HPS study data) is that if you take simvastatin 40 mg for 6 years, your chance of being alive is 87.1% and if you take nothing your chance is 85.3%…….Dr Collins have obviously avoided mentioning these numbers…..

In answer to the question ‘do we expect the public …to pay for studies’, the answer is yes if it means unbiased, open and rigorous research. Monies saved on ineffective or dangerous drugs could conserve rather than waste money.

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